Systematically applied chemicals that damage lung tissue

A large, and increasing number of drugs and chemicals have been found which are toxic to lung following systemic administration. These agents damage lung tissue specifically, or in addition to damage to other tissues. Mechanisms explaining the pulmonary damage produced by some lung toxins have been uncovered. These include concentration of the agent within lung, the absence of adequate pulmonary detoxication systems, and bioactivation to a toxic species within specific lung cells or at distant sites followed by transport to the lung. The basic biochemical lesions underlying lung damage, responses of individual lung cells and pulmonary repair processes to the toxic agent, and species and age differences in susceptibility to lung damage have not, however, been well defined for most lung toxins. This review describes the information available on pulmonary biochemical and pathological changes associated with some of these lung-toxic agents. In addition, mechanisms proposed to explain the lung damage are discussed. The agents covered include: paraquat, the thioureas, butylated hydroxytoluene, the trialkylphosphorothioates, various lung-toxic furans and antineoplastic agents, the pyrrolizidine alkaloids, metals and organometallic compounds, amphiphilic agents, hydrocarbons, oleic acid, 3-methylindole, and diabetogenic agents. Detailed reviews on the overall toxicity of many of these agents have been published elsewhere. This review concentrates on their pulmonary toxicity. Information is presented as an overview to illustrate both the extensive literature that is available and the important questions that remain to be answered about systemic chemicals that damage lung tissue.